PITTSBURGH (AP) - Boston's Tim Wakefield could hear the cheers when he stepped on the mound Saturday night for his first start in Pittsburgh in nearly two decades.

And he heard the largest crowd in PNC Park history grow even louder when the Pirates finally figured out how to handle the 44-year-old's tricky knuckleball.

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Lyle Overbay hit a 3-run homer during a pivotal fourth-inning rally and Joel Hanrahan picked up his 22nd save as Pittsburgh spoiled Wakefield's homecoming with a 6-4 win Saturday night to send the Red Sox to their fourth straight loss.

``I felt great except for the fourth,' Wakefield said. ``It ends up costing us the ballgame.'

Wakefield (4-3) gave up five runs on seven hits in six innings, walking four and striking out two. Pittsburgh did most of its damage in the fourth, scoring four runs to erase a 2-0 deficit. Overbay's sixth homer of the season gave the Pirates the lead and pitcher Jeff Karstens later added the first RBI of his career.

``It just didn't do a whole lot,' Overbay said of the knuckler he deposited in the right field seats. ``You could it see as soon as he threw it (Wakefield) just kind of put his head down. He knew it didn't come out right.'

The converted first baseman was a sensation in Pittsburgh nearly 20 years ago, finishing third in Rookie of the Year voting in 1992 after his signature pitch helped lead the Pirates to within a game of the World Series. He posted a pair of complete-game victories in the National League championship series against the Atlanta Braves that fall.

Wakefield's win in Game 6 of that series remains the last postseason triumph for the Pirates, a franchise that hasn't finished above .500 since, while Wakefield has won two World Series rings during his 17 seasons in Boston.

He was ``grateful' for the round of applause when he was introduced, but was anxious to move on. So are the Red Sox after dropping a half-game behind New York in the AL East standings.

``We can win four just like we lost four, so we're not going to get too up or too down,' said second baseman Dustin Pedroia, who had two hits but also a costly error that led to a Pittsburgh run. ``We started the season 2-10 and we've been kicking (butt) ever since, so I don't think anybody's going to go home and jump out of their hotel room because we lost four in a row.'

Adrian Gonzalez, Josh Reddick and Jacoby Ellsbury all hit solo home runs for the Red Sox, but Boston again could muster no offense when it mattered.

Pittsburgh improved to 35-0 when leading after eight innings behind Hanrahan, who got David Ortiz to ground out to start the ninth then struck out Gonzalez to end the game.

``We looked like we were going to come back, and we just couldn't do it,' said Boston manager Terry Francona. ``Their bullpen just shut us down.'

Boston's nine-game interleague road trip - which includes a visit to Philadelphia starting Tuesday - is off to a bumpy start, though it's hard to blame Gonzalez.

The first baseman continued his torrid hitting against National League pitching. He began the night batting .543 in interleague play, a number that took a bit of a dip even hitting his 16th home run of the season and pushing his major league-leading RBI total to 71.

Karstens (5-4), thrust into a starting role when Ross Ohlendorf went down with a right shoulder injury, has arguably become the team's most durable starter. He pitched into the seventh inning in each of his last five starts and grinded through a season-high 109 pitches against baseball's top offense, giving up four runs, three earned, on six hits while striking out two.

Though he struggled a bit with his command - the three walks he issued were one more than he allowed all month - Karstens managed to avoid the big inning that has fueled Boston's meteoric rise through the standings the last two months.

``We scored just enough runs to get the 'W' and that's what it's all about,' Karstens said.

Notes: Pedroia went 2 for 4 to extend his hitting streak to 10 games. ... Wakefield has started on the road against all but three teams in the majors, Arizona, Washington and the Red Sox. ... The Pirates called up catcher Eric Fryer from Triple-A Indianapolis on Saturday. When he plays he'll become the seventh catcher used by the team this year, the most they've used in one season since 1953. ... Pittsburgh improved to 14-9 in June, assuring the Pirates of their first winning month since June 2009.